18β‐glycyrrhetinic acid attenuates anandamide‐induced adiposity and high‐fat diet induced obesity

SCOPE: Previous reports suggest that licorice extract has various metabolically beneficial effects and may help to alleviate adiposity and hyperlipidemia. However, underlying anti‐obesity mechanisms still remain elusive. Moreover, it is unknown which single ingredient in licorice extract would mediate such effects. We aimed to demonstrate that licorice extract and its active ingredients can inhibit adipocyte differentiation and fat accumulation. METHODS AND RESULTS: 18β‐glycyrrhetinic acid (18β‐GA) alleviated the effects of CB1R agonist, anandamide (AEA) on CB1R signaling in a concentration‐dependent manner. Consistently, 18β‐GA suppressed AEA‐induced adipocyte differentiation in 3T3‐L1 cells through the downregulation of AEA‐induced MAPK activation and expression of adipogenic genes including C/EBP‐α and PPAR‐γ. The protein levels of fatty acid synthase and stearoyl‐CoA desaturase 1 were also decreased and the phosphorylation of acetyl‐CoA carboxylase was increased in 18β‐GA pretreated cells. The supplementation of 18β‐GA significantly lowered body weight, fat weight, and plasma lipids levels in obese animal models. CONCLUSION: These results may provide a novel insight into the molecular mechanism involved in anti‐adipogenic and anti‐obesity effects of 18β‐GA by suppressing the activation of CB1R induced by AEA. Thus, 18β‐GA may exert beneficial effects against obesity‐related metabolic disorders.